SODIUM HYDROSULFITE CONTRACTIONS OF SMOOTH-MUSCLE ARE CALCIUM AND MYOSIN PHOSPHORYLATION-INDEPENDENT

In an effort to further understand the processes underlying hypoxic pu lmonary vasoconstriction, we examined the mechanism by which sodium hy drosulfite (Na2S2O4), a potent reducing agent and oxygen scavenger, in duces smooth muscle contraction. In rat pulmonary arterial strips, sod ium hydrosulfite (10 mlM) induced contractions that were 65.9 +/- 12.8 % of the response to 60 mM KCl (n = 9 segments). Contractions were not inhibited by nisoldipine (5 mu M) or by repeated stimulation with caf feine (10 mM), carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (1 0 mu M), or cyclopiazonic acid (10 mu M), all of which eliminated resp onses to contractile agonists. Maximum force generation after exposure to sodium hydrosulfite was 0.123 0.013 mN in the presence of 1.8 mM c alcium and 0.127 +/- 0.015 mN in the absence of calcium. Sodium hydros ulfite contractions in pulmonary arterial segments were not due to the generation of H2O2 and occurred in the presence of chelerythrine (10 mu M), which blacked phorbol ester contractions, and solution hyperoxy genation. Similar contractile responses were obtained in rat aortic an d tracheal smooth muscles. Finally, contractions occurred in the compl ete absence of an increase in myosin light chain phosphorylation. Ther efore sodium hydrosulfite-induced smooth muscle contraction is not spe cific to pulmonary arterial smooth muscle, is independent of calcium a nd myosin light chain phosphorylation, and is not mediated by either h ypoxia or protein kinase C.